Kravtsov Oleksandr, Hartley Christopher P, Compérat Eva-Maria, Iczkowski Kenneth A
Department of Pathology, Medical College of Wisconsin Milwaukee, WI, USA.
Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie Paris, France.
Am J Clin Exp Urol. 2019 Jun 15;7(3):178-181. eCollection 2019.
Kinesin family member 3B (KIF3B) is a microtubule motor kinesin involved in mitotic progression and vasculotropism. A novel therapeutic target, it is overexpressed in several cancers [PMID 29904055]. Its significance in prostate cancer (PC) was uncertain.
89 cases, including tissue microarrays from 70 prostatectomies comprising matched cancer and benign spots, 19 additional prostatectomy tissues, plus 16 prostate cancer metastases (7 nodal and 9 distant sites; 8 had matched primary PC) were stained with rabbit polyclonal KIF3B antibody. Cytoplasmic immunoreactivity was scored: 0 (negative) to 3+ (strong and diffuse). 39 patients had no nodal metastases, 31 had positive lymph nodes, and 19 had nodes not sampled. Gleason grade groups were 1 (9), 2 (28), 3 (39), 4 (1), and 5 (12). 15 cases had cribriform pattern. AJCC stages were 2 (48), 3 (29), unknown (12).
KIF3B in PC (mean 1.0) was higher than in benign prostate (mean 0.1, P<0.01, Student t-test). All 7 available nodal metastases of PC were negative. One-third of primary PCs with nodal metastases lost all expression, compared to retained expression in all but one PC without nodal metastasis (P<0.01, chi-square). The former group also had stronger staining (mean 1.0) than metastases (mean 0.3) (P<0.01, Student t-test) and had fewer cases with any positive (>0) expression compared to cases without metastases or with unsampled lymph nodes (P<0.01, chi-square test). Reactivity of paired metastatic tissue and primary PC correlated strongly (Pearson coefficient: +0.7). No significant trends were found by grade group, cribriform status, or stage.
KIF3B is a PC marker. Metastatic cancers showed less KIF3B expression than their primary PC counterparts, and primary cases with positive nodes demonstrated reduced positivity, suggesting use as a prognostic marker. It is possible that KIF3B protein becomes altered prior to metastases, preventing immunohistochemical detection.
驱动蛋白家族成员3B(KIF3B)是一种参与有丝分裂进程和向血管性的微管驱动蛋白。作为一种新的治疗靶点,它在多种癌症中过表达[PMID 29904055]。其在前列腺癌(PC)中的意义尚不确定。
89例样本,包括来自70例前列腺切除术的组织芯片(包含配对的癌组织和良性组织)、另外19例前列腺切除组织,以及16例前列腺癌转移灶(7例淋巴结转移和9例远处转移;8例有配对的原发性PC),用兔多克隆KIF3B抗体进行染色。对细胞质免疫反应性进行评分:0(阴性)至3+(强且弥漫)。39例患者无淋巴结转移,31例有阳性淋巴结,19例未取淋巴结样本。Gleason分级组为1级(9例)、2级(28例)、3级(39例)、4级(1例)和5级(12例)。15例有筛状结构。美国癌症联合委员会(AJCC)分期为2期(48例)、3期(29例)、分期不明(12例)。
PC中KIF3B(平均值1.0)高于良性前列腺组织(平均值0.1,P<0.01,学生t检验)。PC的所有7例可用淋巴结转移灶均为阴性。有淋巴结转移的原发性PC中有三分之一失去了所有表达,相比之下,除1例无淋巴结转移的PC外,其余所有PC均保留表达(P<0.01,卡方检验)。前一组的染色也比转移灶更强(平均值1.0)(平均值0.3)(P<0.01,学生t检验),与无转移或未取淋巴结样本的病例相比,任何阳性(>0)表达的病例更少(P<0.01,卡方检验)。配对的转移组织和原发性PC的反应性密切相关(皮尔逊系数:+0.7)。按分级组、筛状结构状态或分期未发现显著趋势。
KIF3B是一种PC标志物。转移性癌组织中KIF3B表达低于其原发性PC对应组织,有阳性淋巴结的原发性病例显示阳性率降低,提示可作为预后标志物。有可能KIF3B蛋白在转移前发生改变,从而无法通过免疫组织化学检测到。